smaerd
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Registered: 23-1-2010
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Mood: hmm...
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Chiral Resolution Idea Input Please :)
So I'm aware that for Protein Stationary Phases they tend to bond a quaternary ammonium salt directly to silica/stationary phase through coupling and
ionic interactions(Chiral Chromatography page 268 by: T.E. Beesley and R.P.W. Scott).
Now this could be a totally bogus idea, and if it is I don't need a huge write-up as to why just a quick explanation.
In a typical column chromatography column...
Would it be possible to use something such as {amino protected} D or L tryptophan and couple the acid moiety to trimethylamine using
dicyclohexylcarbodiimide{DCC}(perhaps a little HOBT to inhibit epimerization/racemization though it is not common with amino acids with this reagent).
Then deprotection of course.
This quat. would then have a tendency to loom on silica via ionic attraction as well base attraction(so it could be used with non-polar solvents
without much "leakage"). It would with-hold it's D or L nature(for the most part), hopefully providing a decent separation of a given enantiomer. It
would be cheaply made. The idea is to maybe use an extra inch(~2.5cm) of "un-doped" silica underneath the "doped" silica so even if the quat trails a
bit it has some extra room before elution.
Though perhaps sillica isn't the ideal stationary phase, I am aware activated carbon really enjoys adsorbing ionic moeties(which Q.A.S. are). Any
input/ideas? Granted this is vague indeed, no desired racemate to resolve, etc. In theory though could this work to provide enantiomer resolutions?
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fledarmus
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Registered: 23-6-2011
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Immobilized natural amino acids are certainly possible, and useful. See for example:
Removing metals using immobilized amino acids
In certain, very limited circumstances, they have been used for chiral separations, eg.:
Electrokinetic separation of chiral compounds
The problem is that a single natural amino acid doesn't present a particularly chiral environment. It is the use of long chains of amino acids that
make enzymes so exquisitely sensitive to chirality.
The first of the really effective general use chiral columns, the Pirkle columns, used some very highly functionalized amino acids to get good
resolution. (see William H. Pirkle and John M. Finn, J. Org. Chem. 1981,46, 2935-2938 Chiral High-pressure Liquid Chromatographic Stationary
Phases. 3. General Resolution of Arylalkylcarbinols). Rather than immobilizing their amino acids directly to the silica gel, however, they
attached an aminopropyl group to the silica and ionically bonded the amino acid to the aminopropyl group. In his early work he experimented with
attaching the chiral stationary phase directly to the silica gel, but his separations were better when the chiral material was somewhat further from
the silica. He also speculated that the uncapped silica was interfering with the separation and experimented with capping any exposed silica gel to
prevent that. He wanted the only polar interactions to occur through the chiral stationary phase rather than the support. I believe the choice of an
ionic interaction to hold the chiral phase in place rather than a covalent one was to make it easier to synthesize and characterize his stationary
phases - he could add his chiral substrate to an already-packed column of aminopropyl-capped silica gel, wash and dry the column, then immediately use
it for separations, as long as the ionic strength of the solvent was weak enough that it didn't disrupt the bonds between the aminopropyl group and
his chiral substrate.
There is some use of polymerized amino acids and immobilized proteins in HPLC, but they tend to be for very specific compounds and the amino acid or
protein would have to be reoptimized for every type of molecule being separated. Sugars and starches present a more chiral environment for separation
and are more general to the types of compounds being separated.
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